Vitamin D inadequacy: the Italian picture. Possible consequences of hypovitaminosis D observed in Italy

hypovitaminosis D observed in Italy

Vitamin D is essential for maintaining calcium homeostasis and optimising bone health. Low concentrations of vitamin D lead to alterations in calcium and phosphorus homeostasis, sec­ondary hyperparathyroidism, bone loss, osteoporosis, and an increase in fracture risk. More severe degrees of vitamin D de­ficiency lead to impairment of bone mineralization and osteo- malacia.

In 1990 we observed that in the patients with serum levels of 25OHD lower than 10 ng/mL the incidence of hypocalcaemia was significantly raised (p < 0.03).

Bettica et al. reported that in subjects with hypovitaminosis D PTH was significantly increased (p < 0.05), while mean val­ues of femoral bone mineral density (BMD), 24-h urinary calci­um and osteocalcin were significantly lower (p < 0.05) than those found in subjects with normal vitamin D status. There was no difference between groups as regards to mean age and mean lumbar BMD. Moreover, in a subgroup of 23 women who were comparable to other subjects for all the parameters considered, the Authors found a significant positive correlation between 1,25(OH)2D and 25OHD serum levels (r = 0.49, p < 0.03), while no correlations were found between 1,25(OH)2D and age, creatinine clearance and PTH.

Recently Pepe et al. investigated the relative contribution of the major factors regulating calcium homeostasis in deter­mining the circulating levels of PTH in healthy women and men. 25OHD was the main explicative variable almost in every multiple linear regression model, both considering the group as a whole and when considering men and women separately. In subjects with vitamin D insufficiency (25OHD < 30 nmol/L), mean serum levels of parathyroid hormone were significantly higher (P < 0.001) than those in subjects of similar age with normal vitamin status. This study demonstrates the central role of 25OHD in regulating PTH secretion in physiological condi­tions.

Also in the study of Isaia et al. 25OHD and PTH levels were strongly correlated: the best correlation coefficient was ob­tained after logarithm transformation of both variables (r = -0.38). Thirty-eight percent of the women with serum vitamin D below 12,5 nmol/L had PTH levels above 45 pg/mL, a value that corresponds to the 95th percentile of PTH distribution in normal healthy young subjects. Values of PTH above 45 pg/mL were found in only 8% of the women with 25OHD levels above 30 nmol/L. The relationship between vitamin D status and PTH is very similar to that found by others with a “breaking point” around 33 ng/mL. A confounder may be the dietary calcium in­take, which influences serum PTH: the increase in serum PTH in the case of low serum 25OHD may be less prominent when calcium intake is high. In this study dairy calcium intake was re­ported positively associated with 25OHD levels. This observa­tion indicates that in a large proportion of the patients hypovita- minosis D is associated with low calcium intake, exacerbating the metabolic skeletal consequences.

Carnevale et al., by subdividing samples according to serum 25OHD levels (either lower or higher than 30 nmol/L), observed higher PTH (p < 0.02) in subjects with lower values of 25OHD. In both sexes summer 25OHD levels were higher, while PTH values were significantly lower. Male subjects did not display hypovitaminosis D, having throughout the year sig­nificantly higher calcium and 25OHD levels together with lower PTH values, than women. In the whole sample, serum 25OHD correlated positively with serum calcium and inversely with PTH. Moreover, the seasonal percentage variations in PTH were inversely correlated with those of urinary calcium excre­tion. Only in women, during winter when serum levels of 25OHD are lower, bone remodelling markers (serum alkaline phosphatase, urinary pyridinoline and deoxypyridinoline) were described higher while urinary calcium levels were lower than in summer. Higher PTH and urinary deoxypyridinoline levels were observed in subjects with lower values of 25OHD. This data shows significant gender-specific differences in both calci­um homeostasis and skeletal remodelling indexes; the season­al fluctuations in the vitamin D-PTH axis are accompanied by cyclical variations of bone turnover rate, which were more pro­nounced in women.

Passeri et al. in centenarians affected by severe hypovita- minosis D observed that PTH and serum C-terminal fragment of collagen type I were elevated in 64 and 90% of subjects, re­spectively, with a trend toward hypocalcaemia; bone alkaline phosphatase levels were close to the upper limit. In these pa­tients ultrasonographic bone parameters were correlated with resorption markers. Authors conclude that the extreme decades of life are characterized by a sequence of events linking vitamin D deficiency, low serum calcium, and secondary hyperparathy­roidism with an increase in bone resorption and severe os­teopenia. Higher levels of 25OHD are required in older com­pared to younger persons to avoid the age-associated com­pensatory hyperparathyroidism.

As expected by pathophysiology, numerous authors have found a relationship between vitamin D status and BMD. A re­cent study on this topic has been carried out on 156 Italian postmenopausal women. Malavolta et al. found a positive statistically significant correlation between BMD, both at the spine and hip, and 25OHD, and a negative statistically signifi­cant correlation between BMD and PTH. No statistically signifi­cant correlation was found between BMD and 1,25(OH)2D. Crude logistic regression showed age, 25OHD and PTH were significant predictors of low BMD, while 1,25(OH)2D was not. Backward logistic regression showed 25OHD was the best pre­dictive model for spine osteoporosis together with age, and alone it was the best predictive model for femoral neck osteo­porosis.

Del Puente et al. investigated the predictive value of serum 25OHD levels and other clinical variables for BMD changes in healthy women participating in a population-based longitudinal study carried out in Napoli. 139 women (45 to 79 years of age) were examined at study entry and then again af­ter two years (24 ± 2 months) following the same protocol. They underwent medical examination, questionnaire, anthropo- metric measurements, blood sampling and urine collection; BMD was measured by dual energy X-ray absorptiometry at the lumbar spine and femoral neck. The results indicated that the serum 25OHD level was the only independent determinant of BMD variations at the femoral site.

Isaia et al. observed that the mean age-adjusted 25OHD values were significantly (P < 0.05) lower in the 25 women who sustained a hip fracture (17.7 ± 5,5 nmol/L) than in all the oth­ers (27,5 ± 24,7 nmol/L). Such a difference was not found for any other fracture. The prevalence of hip fracture was 5.8% in subjects with 25OHD levels lower that 12,5 nmol/L, and 3.9% in women with 25OHD levels ranging from 12,5 to 30 nmol/L; none of the subjects with 25OHD levels greater that 30 nmol/L had a history of hip fracture. Moreover women with low 25OHD levels (< 30 nmol/L) had worse scores for daily living activities (ADL) and mobility ADL (move outdoors, use stairs, walk at least 400 m, carry a heavy object). However, given the cross- sectional nature of this study, we cannot rule out the opposite causal relationship, i.e. that patients with a poorer ADL score or prior fracture are at greater risk of hypovitaminosis. In any event, these results indicate that prior hip fracture represents a paradoxical risk factor for hypovitaminosis D! Recently Di Monaco et al. evaluated the association be­tween serum levels of 25OHD and functional recovery after hip fracture in a cross-sectional study. A total of 350 hip-fracture patients consecutively admitted to a rehabilitation hospital were investigated; thirty-five patients were excluded because their hip fracture was caused by major trauma or cancer affecting the bone or they could not complete rehabilitation. Patients un­derwent 25OHD assessment at a mean of 21.3 ± 8.1 days after the hip fracture; functional recovery was evaluated by using Barthel Index scores. Low levels of 25OHD were generally found (median, 17 nmol/L). By using the Spearman rank corre­lation test, a significant positive correlation was observed be­tween serum 25OHD and Barthel Index score assessed on ad­mission (rho = .218, P < .001) and discharge (rho = .198, P < .001), but not with the change in Barthel Index score attribut­able to rehabilitation. Linear multiple regression showed that the association between 25OHD and Barthel Index score was independent of 11 confounding variables: age, sex, hip-fracture type, pressure ulcers, cognitive impairment, neurological im­pairment, infections, time between fracture occurrence and 25OHD evaluation, co-morbidity, surgical procedure type, and previous hip fractures. Make your pharmacy dollar go further and Purchase Cialis online

The relationships between vitamin D, functional status, and disability in a sample of elderly, community-dwelling subjects was investigated in Italy by Zamboni et al.. Serum values of 25OHD and albumin were determined in all participants. An- thropometric measures were obtained, and body composition was assessed using dual-energy X-ray absorptiometry. Arm and leg isometric strength was tested. Reported disability was evaluated using a modified version of the Activities of Daily Liv­ing Scale and physical performance with the 6-minute walking test and two items of the Short Form 36 Health Survey Ques­tionnaire (SF-36). A significantly higher prevalence of hypovita­minosis D, defined as level of 25OHD < 37.5 nmol/L, was ob­served in women than in men (55.4% and 35.1%, respectively; p < .001). In women, 25OHD was significantly associated with muscular strength and levels of physical function as assessed by SF-36. After adjusting for body mass index, albumin, appen- dicular fat-free mass, and season, muscle strength was still significantly lower in women with hypovitaminosis D than in those without. Women with reported disability showed signifi­cantly lower 25OHD values than those without. No relationship between muscular strength, physical function, or reported dis­ability and 25OHD was found in men. Therefore in community- dwelling elderly women, 25OHD is related to muscular function and reported disability; because of the high prevalence of hy- povitaminosis D in the elderly population, this association seems to be clinically relevant.

Category: Health

Tags: hip fracture, osteoporosis, PTH, vitamin D

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